Newer ICU Ventilation Strategies Hold No Survival Benefit

Action Points

Explain to interested patients that the findings of these two studies may support higher PEEP ventilation strategies despite a lack of mortality benefit.

Note that both studies found the experimental ventilation strategies to be safe.

HAMILTON, Ontario, Feb. 12 -- Variations on low-tidal-volume ventilation using higher positive end-expiratory pressure (PEEP) to open the lungs of critically ill patients may have only secondary benefits, researchers found here and in France.

An investigational strategy adding recruitment maneuvers and high levels of PEEP to established low-tidal-volume ventilation failed to improve overall hospital mortality or barotrauma for patients with acute lung injury, according to findings of the large Lung Open Ventilation (LOV) trial.

However, the "open lung" strategy held advantages for secondary hypoxemia and rescue therapy endpoints, Maureen O. Meade, M.D., of McMaster University here, and colleagues reported in the Feb. 13 issue of the Journal of the American Medical Association.

Likewise in the Expiratory Pressure (Express) Study, a higher level of PEEP to increase lung recruitment improved lung function and duration of organ failure but not mortality compared with a moderate PEEP strategy aimed at minimal distension, found Alain Mercat, M.D., of CHU d'Angers in Angers, France, and colleagues reported in the same issue of JAMA.

Although it might appear that the level of PEEP in an unselected population of patients with acute lung injury does not matter, "this is not the end of the story," wrote Luciano Gattinoni, M.D., and Pietro Caironi, M.D., of the Universita degli Studi di Milano in Milan, Italy, in an accompanying editorial.

Rather, the studies indicate that higher levels of PEEP are safe and probably beneficial and now need to be tested in more selected patient populations, such as those with greater lung edema and recruitability, they said.

The LOV trial compared the new ventilation strategy with conventional ventilation in 983 consecutive patients at 30 ICUs in Canada, Australia, and Saudi Arabia who had acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. Among them, 85% met criteria for acute respiratory distress syndrome (ARDS) at enrollment.

Rescue therapy use was less common with open lung ventilation than with the conventional strategy both among patients who met eligibility criteria (5.1% versus 9.3%, P=0.045) and overall (7.8% versus 12%, P=0.05).

The Express study further tested strategies to control PEEP titrated by plateau pressure rather than oxygenation. It included 767 adults with acute lung injury treated at 37 intensive care units in France.

The 382 participants randomized to a minimal distension strategy were treated with a moderate PEEP target of 5 to 9 cm H2O (mean 8.4 cm H2O with a plateau pressure of 21.1 cm H2O).

The 385 patients randomized to an increased recruitment strategy received PEEP with a target plateau pressure of 28 to 30 cm H2O (mean 15.8 cm H2O on day one with a plateau pressure of 27.5 cm H2O).

All patients received ventilation with a tidal volume set at 6 mL/kg of predicted body weight.

For the primary endpoint, 28-day mortality was lower, but not significantly so, in the increased recruitment group compared with minimal distension (27.8% versus 31.2%, RR 1.12, P=0.31). In-hospital and 60-day mortality were similar between groups as well.

However, the increased recruitment group had more than twice as many ventilator-free days (median seven versus three, P=0.04) and organ failure-free days (median six versus two, P=0.04) at 28 days.

Fewer patients in the increased recruitment group required rescue therapy for severe hypoxemia than in the minimal distension group (18.7% versus 34.6%, P<0.001).

The increased recruitment ventilation strategy also was associated with higher respiratory system compliance values and better oxygenation, but modestly greater fluid requirements, which "possibly reflected poor tolerance of higher levels of PEEP in some patients."

The lack of mortality benefit may have been because benefit for some patients was offset by harm to others, both research groups said.

In the end though, the studies support the newer ventilation strategies as an acceptable alternative to the current standard of care, Dr. Meade and colleagues said.

Drs. Gattinoni and Caironi agreed that the findings favor use of higher levels of PEEP in the early phase of acute lung injury and ARDS.

Until direct assessment of lung recruitability by dynamic lung imaging is widely available, they said, "setting PEEP at the highest level compatible with a plateau pressure of 28 to 30 cm H2O and a tidal volume of 6 mL/kg of predicted body weight seems to be a reasonable alternative."

However, another accompanying editorial by Jean-Daniel Chiche, M.D., of the University Rene Descartes in Paris, and Derek C. Angus, M.D., M.P.H., of the University of Pittsburgh, cautioned about the unblinded treatment in both studies.

Furthermore, "it is impossible to know whether any of these protocols outperform expert-directed ventilator management," they noted, and inferences can be drawn only for the intervention as a whole rather than being attributed specifically to the level of PEEP.

The LOV study was supported by grants from the Canadian Institutes for Health Research and Hamilton Health Sciences Foundation. Dr. Meade was a Peter Lougheed Scholar of the Medical Research Council of Canada and two co-authors were clinical trials mentors for the Canadian Institutes of Health Research, but the authors reported no conflicts of interest.

The Express study was funded by the Centre Hospitalier Universitaire d'Angers and supported by a grant from the MinistÃ¨re de la santeÂ´ and a research grant from the Association National pour le Traitement Ã Domicile de l'Insuffisance Respiratoire. The researchers reported no conflicts of interests.

The editorialists reported no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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